Application of Fuzzy Control in a Photovoltaic Grid-Connected Inverter

To realize the maximum power output of a grid-connected inverter, the MPPT (maximum power point tracking) control method is needed. The perturbation and observation (P&O) method can cause the inverter operating point to oscillate near the maximum power. In this paper, the fuzzy control P&O method is proposed, and the fuzzy control algorithm is applied to the disturbance observation method. The simulation results of the P&O method with fuzzy control and the traditional P&O method prove that not only can the new method reduce the power loss caused by inverter oscillation during maximum power point tracking, but also it has the advantage of speed. Inductive loads in the post-grid-connected stage cause grid-connected current distortion. A fuzzy control algorithm is added to the traditional deadbeat grid-connected control method to improve the quality of the system’s grid-connected operation. The fuzzy deadbeat control method is verified by experiments, and the harmonic current of the grid-connected current is less than 3%

Autophagy enhances the replication of Peste des petits ruminants virus and inhibits caspase-dependent apoptosis in vitro

Peste des petits ruminants (PPR) is an acute and highly contagious disease in small ruminants that causes significant economic losses in developing countries. An increasing number of studies have demonstrated that both autophagy and apoptosis are important cellular mechanisms for maintaining homeostasis, and they participate in the host response to pathogens. However, the crosstalk between apoptosis and autophagy in host cells during PPRV infection has not been clarified. In this study, autophagy was induced upon virus infection in caprine endometrial epithelial cells (EECs), as determined by the appearance of double- and single-membrane autophagy-like vesicles, LC3-I/LC3-II conversion, and p62 degradation. We also found that PPRV infection triggered a complete autophagic response, most likely mediated by the non-structural protein C and nucleoprotein N. Moreover, our results suggest that autophagy not only promotes the replication of PPRV in EECs but also provides a potential mechanism for inhibiting PPRV-induced apoptosis. Inhibiting autophagosome formation by wortmannin and knocking down the essential autophagic proteins Beclin-1 and ATG7 induces caspase-dependent apoptosis in EECs in PPRV infection. However, inhibiting autophagosome and lysosome fusion by NH4Cl and chloroquine did not increase the number of apoptotic cells. Collectively, these data are the first to indicate that PPRV-induced autophagy inhibits caspase-dependent apoptosis and thus contributes to the enhancement of viral replication and maturity in host cells

A novel GTP-binding inhibitor, FX2149, attenuates LRRK2 toxicity in Parkinson's disease models.

Leucine-rich repeat kinase-2 (LRRK2), a cytoplasmic protein containing both GTP binding and kinase activities, has emerged as a highly promising drug target for Parkinson's disease (PD). The majority of PD-linked mutations in LRRK2 dysregulate its GTP binding and kinase activities, which may contribute to neurodegeneration. While most known LRRK2 inhibitors are developed to target the kinase domain, we have recently identified the first LRRK2 GTP binding inhibitor, 68, which not only inhibits LRRK2 GTP binding and kinase activities with high potency in vitro, but also reduces neurodegeneration. However, the in vivo effects of 68 are low due to its limited brain penetration. To address this problem, we reported herein the design and synthesis of a novel analog of 68, FX2149, aimed at increasing the in vivo efficacy. Pharmacological characterization of FX2149 exhibited inhibition of LRRK2 GTP binding activity by ~90% at a concentration of 10 nM using in vitro assays. Furthermore, FX2149 protected against mutant LRRK2-induced neurodegeneration in SH-SY5Y cells at 50-200 nM concentrations. Importantly, FX2149 at 10 mg/kg (i.p.) showed significant brain inhibition efficacy equivalent to that of 68 at 20 mg/kg (i.p.), determined by mouse brain LRRK2 GTP binding and phosphorylation assays. Furthermore, FX2149 at 10 mg/kg (i.p.) attenuated lipopolysaccharide (LPS)-induced microglia activation and LRRK2 upregulation in a mouse neuroinflammation model comparable to 68 at 20 mg/kg (i.p.). Our results highlight a novel GTP binding inhibitor with better brain efficacy, which represents a new lead compound for further understanding PD pathogenesis and therapeutic studies

Chemerin: A Functional Adipokine in Reproductive Health and Diseases

As a multifaceted adipokine, chemerin has been found to perform functions vital for immunity, adiposity, and metabolism through its three known receptors (chemokine-like receptor 1, CMKLR1; G-protein-coupled receptor 1, GPR1; C-C motif chemokine receptor-like 2, CCRL2). Chemerin and the cognate receptors are also expressed in the hypothalamus, pituitary gland, testis, ovary, and placenta. Accumulating studies suggest that chemerin participates in normal reproduction and underlies the pathological mechanisms of certain reproductive system diseases, including polycystic ovary syndrome (PCOS), preeclampsia, and breast cancer. Herein, we present a comprehensive review of the roles of the chemerin system in multiple reproductive processes and human reproductive diseases, with a brief discussion and perspectives on future clinical applications

Autophagy enhances the replication of Peste des petits ruminants virus and inhibits caspase-dependent apoptosis in vitro

<p>Peste des petits ruminants (PPR) is an acute and highly contagious disease in small ruminants that causes significant economic losses in developing countries. An increasing number of studies have demonstrated that both autophagy and apoptosis are important cellular mechanisms for maintaining homeostasis, and they participate in the host response to pathogens. However, the crosstalk between apoptosis and autophagy in host cells during PPRV infection has not been clarified. In this study, autophagy was induced upon virus infection in caprine endometrial epithelial cells (EECs), as determined by the appearance of double- and single-membrane autophagy-like vesicles, LC3-I/LC3-II conversion, and p62 degradation. We also found that PPRV infection triggered a complete autophagic response, most likely mediated by the non-structural protein C and nucleoprotein N. Moreover, our results suggest that autophagy not only promotes the replication of PPRV in EECs but also provides a potential mechanism for inhibiting PPRV-induced apoptosis. Inhibiting autophagosome formation by wortmannin and knocking down the essential autophagic proteins Beclin-1 and ATG7 induces caspase-dependent apoptosis in EECs in PPRV infection. However, inhibiting autophagosome and lysosome fusion by NH₄Cl and chloroquine did not increase the number of apoptotic cells. Collectively, these data are the first to indicate that PPRV-induced autophagy inhibits caspase-dependent apoptosis and thus contributes to the enhancement of viral replication and maturity in host cells.</p

FX2149 reduced LPS-induced microglia activation and LRRK2-upregulation.

<p>G2019S-LRRK2 BAC transgenic mice (6–12 weeks) were injected with LPS (5 μg) and FX2149 (10 mg/kg) as described in the methods section. Serial coronal sections through the substantia nigra were subjected to immunohistochemistry analysis. A. Representative immunofluorescent images with anti-isolectin (green) and anti-LRRK2 (red) staining. B. Quantification of immunofluorescence of A by unbiased stereology. *<i>p</i> < 0.05 by ANOVA compared with vehicle group. ^#<i>p</i> < 0.05 by ANOVA compared with LPS treated group. C. Representative immunostaining with anti-phospho-LRRK2-S935 and anti-isolectin B4 (marker for microglia) antibodies by DAB detection.</p

FX2149 improved the brain penetration and inhibition of LRRK2 GTP binding and kinase activities.

<p>FX2149 (10 mg/kg) and 68 (10 and 20 mg/kg) were injected intraperitoneally into G2019S-LRRK2 BAC transgenic mice at 6–12 weeks of age for 1 hour. There were 6 mice in each experimental group. The brain homogenates were used to detect LRRK2 GTP-binding and kinase activities. A and B, LRRK2 GTP-binding assays. C and D, LRRK2 phosphorylation assays using anti-phospho-LRRK2 antibodies. E and F, FX2149 reduced G2019S-LRRK2-induced 4E-BP phosphorylation determined by anti-phospho-4E-BP western blot analysis. Ntg: non-transgenic mouse. *<i>p</i> < 0.05 by ANOVA compared with G2019S-LRRK2 transgenic mice treated with vehicle.</p

FX2149 inhibits LRRK2 GTP binding activity.

<p>WT or mutant LRRK2 was pulled down from lysates of transfected HEK293T cells using GTP-agarose in the absence or presence of FX2149 at 1 and 10 nM concentrations. The resulting precipitates were subjected to western blot analysis using anti-Flag antibodies. A and C. Representative blots from GTP binding assays. B and D. Quantification of A and C. K1347A-LRRK2, non GTP binding genetic control. All experiments were repeated three times with similar results. *<i>p</i><0.05 by ANOVA, <i>vs</i> vehicle control.</p